Objective: The aim of this study was to investigate in vitro and in vivo behavior of the prepared ethosomal formulations of green tea extract, which in turn would result in enhancing their therapeutic efficacy as antioxidants and thermogenic agents in obese mice. Methods: Fat Wistar rats were acclimated for at least 7 d in environmentally controlled cages, then they were divided into five groups: 1st received only distilled water, 2nd received an oral dose of green tea extract, in 3rd group green tea extract loaded gel base was applied on the previously shaven dorsal side of rats and in the other 2 groups selected green tea extract loaded Ethosomal gel base were applied on the previously shaven dorsal side of rats. Total antioxidant capacity by ferric reducing ability of plasma (FRAP) method, catalase enzyme activity, malondialdehyde (MDA) and thiobarbituric acid reactive substance (TBARs) levels, and real-time qPCR of UCP2 and 3 were then determined. Results: Formulation of green tea extract as ethosomal preparations exhibited a controlled release rate due to the reservoir action of ethosomes. The levels of TBARs and MDA were lower in groups supplemented with green tea extracts compared to control group and in groups (3-5) received it transdermal (P<0.0001 in all 3 groups) was lower than group received it orally with P = 0.0081. The messenger RNA levels of UCPs 2 and 3 in BAT were increased in those 3 groups. Conclusion: The results support the efficiency of ethosomal gel in penetrating the lipid rich biological membrane. The in vivo study confirms the antioxidant and thermogenic behavior of transdermal applied green tea extract.